In the medical field, where beneficial agents are collected, processed and stored in containers, transported and ultimately delivered through tubes by infusion to patients, there has been a recent trend toward developing materials useful for fabricating such containers and tubing without the disadvantages of currently used materials such as polyvinyl chloride. These new materials for tubing must have a unique combination of properties, so that the tubing may be used in fluid administration sets and with medical infusion pumps. Among these properties are the materials must be optically clear, environmentally compatible, have sufficient yield strength, elasticity and flexibility, have a minimum quantity of low molecular weight additives and other extractables, and be compatible with medical solutions.
It is desirable for medical tubing to be optically transparent to allow for visual inspection of fluids in the tubing. It is also desirable for the tubing to be optically and ultrasonically transparent as it increases the compatability of the tubing with medical infusion pumps. Medical infusion pumps are equipped with ultrasonic sensors for detecting abnormal conditions in the tubing such as air bubbles.
It is also a requirement that the tubing be environmentally compatible as a great deal of medical tubing is disposed of in landfills and through incineration. For tubing disposed of in landfills, it is desirable to use as little material as possible to fabricate the tubing. Further benefits are realized by using a material which is thermoplastically recyclable so that scrap generated during manufacturing may be incorporated into virgin material and refabricated into other useful articles.
For tubing that is disposed of by incineration, it is necessary to use a material that does not generate or minimizes the formation of by-products such as inorganic acids which may be environmentally harmful, irritating, and corrosive. For example, PVC may generate objectionable amounts of hydrogen chloride (or hydrochloric acid when contacted with water) upon incineration.
To be compatible with medical solutions, it is desirable that the tubing material be free from or have a minimal content of low molecular weight additives such as plasticizers, stabilizers and the like. These components could be extracted by the therapeutic solutions that come into contact with the material. The additives may react with the therapeutic agents or otherwise render the solution ineffective. This is especially troublesome in bio-tech drug formulations where the concentration of the drug is measured in parts per million (ppm), rather than in weight or volume percentages. Even minuscule losses of the bio-tech drug can render the formulation unusable. Because bio-tech formulations can cost several thousand dollars per dose, it is imperative that the tubing material be inert.
Polyvinyl chloride ("PVC") has been widely used to fabricate medical tubing as it meets most of these requirements. PVC tubing is optically clear to allow for visual inspection of the fluid flowing through it. PVC tubing has proven to work well in pump administration sets. PVC medical tubing also has desirable stress-strain characteristics so that the material may be stretched to a certain degree along a longitudinal axis of the tubing without causing a significant permanent reduction in the diameter of the tubing. In other words, PVC tubing resists necking. PVC medical tubing also has favorable surface characteristics to allow for controlling the flow rate of fluid through the tubing using slide clamps which operate by crimping the sidewall of the tubing to stop or reduce the flow of fluid through the tubing. The slide clamp may be used without causing scoring or cutting of the tubing.
Because PVC by itself is a rigid polymer, low molecular weight components known as plasticizers must be added to render PVC flexible. As set forth above, in some instances these plasticizers may be extracted out of the tubing by fluid passing through the tubing. For this reason, and because of the difficulties encountered in incinerating and recycling PVC, there is a desire to replace PVC medical tubing.
Polyolefins and polyolefin alloys have been developed which meet many of the requirements of medical containers and tubing, without the disadvantages associated with PVC. Polyolefins typically are compatible with medical applications because they have minimal extractability to fluids. Most polyolefins are environmentally sound as they do not generate harmful degradants upon incineration, and in most cases are capable of being thermoplastically recycled. Many polyolefins are cost effective materials that may provide an economic alternative to PVC. However, there are many hurdles to overcome to replace all the favorable attributes of PVC with a polyolefin.
For example, problems have been encountered in using certain polyolefins to fabricate medical tubing. Such tubing has been found to have poor surface characteristics so that it is readily susceptible to cutting, shredding or scoring when clamping the tubing using a slide clamp. Certain polyolefin tubing also presents difficulties during use in pump pressurized administration sets where the pump controls the flow rate of fluid through the tubing by consecutively impinging upon the sidewalls of the tubing to deliver a precise amount of fluid over a given time period.
Pumps that are used to infuse beneficial agents to patients typically have various sensors to detect such conditions as back pressure of fluid in the tubing, and air bubbles in the fluid stream. The sensors deactivate the pump upon detecting an unacceptable back pressure or an air bubble. The sensors usually have a sensor body in which a segment of the tubing of the administration set is secured in place. It has been found that there is a tendency for the polyolefin tubing to deform when placed in the sensor body due to resistance with side walls of the sensor housing. This deformation in some cases leads the detectors to indicate an abnormal condition and to inappropriately deactivate the infusion pump.
Further, certain polyolefin tubing has been found to have low yield strength. Because there is a direct relationship between yield strength and modulus, it is very difficult to increase the yield strength without increasing at the same time the modulus of the material. In polyolefin materials, the modulus is primarily dependent on crystallinity. In PVC materials, the modulus is primarily dependent on the amount of plasticizer added. When the modulus of the polyolefin material is selected to match that of the plasticized PVC, the polyolefin material's yield strength becomes significantly reduced, and the resulting tubing has too low a yield strength to resists potentially external pulling forces that can result in necking of the tubing. Conversely, when the yield strength is matched with PVC the resultant modulus is too high to function with pumps.
Polyolefin tubing exhibiting low yield strengths are readily susceptible to a phenomenon which is referred to as necking. Necking is a localized reduction in the diameter of the tubing that occurs upon stretching the tubing under moderate strain along the longitudinal axis of the tubing. Necking can cause a reduction in the flow of fluid through the tubing thereby rendering the tubing ineffective.
Applicants have found that it is possible to increase the tubing's resistance to necking by pre-orienting the tubing along the longitudinal axis of the tubing. However, the orientation process may lead to dimensional instability. In particular, oriented polyolefin tubing experiences a phenomenon known as heat recovery, which is sometimes referred as the "memory effect." Heat recovery is a complicated phenomenon that occurs when oriented tubing is heated above the temperature reached during the orientation process. When this occurs the tubing loses its orientation causing shrinking and dimensional changes of the tubing.
In addition, Applicants have found that most medical tubings undergo some permanent deformation when subjected to the long term (24 hours), repetitive, cyclic stresses introduced by pumping mechanisms such as Baxter's FLO-GARD.RTM. 6000 Series pumps. Over this long term use, the deformation causes a variance in the solution delivery rate from the initial rate. This is especially true for polyolefin tubing with low crystallinity.
Polyolefin tubing have also been shown to have poor thermal stability during storage, transportation, and end applications. The poor thermal stability of polyolefin tubing can lead to changes in the desired dimensions and shape. These dimensional and shape changes can possibly adversely affect the accuracy of fluid volume delivery. It can also lead to shape changes that can render the tubing incompatible or difficult to use with pumps. One such problem occurs when tubing, which is frequently stored and shipped in a coiled state, becomes set in that coiled shape. Such coiled tubing is difficult to use as it has the tendency to return to a coiled shape.
One method of improving the thermal stability of non-PVC, polyolefin materials was contemplated in U.S. Pat. No. 4,465,487 issued to Nakamura et al. and assigned to Terumo Kabushiki Kaisha of Japan ("Nakamura"). Nakamura relates to a container for medical use produced from a polyolefin material. More particularly, Nakamura relates to a medical container produced from an ethylene-vinyl acetate (EVA) copolymer containing 10 to 35 weight percent of vinyl acetate cross-linked using an electron beam supplied at 50 to 200 kGys to achieve an EVA copolymer having a gel content of 50% or more. (Col. 3, lines 40-46). The material is cross-linked so that the container can withstand temperatures reached during steam sterilization. However, the resulting high gel content of the material caused by a high dose of radiation renders the material a thermoset by nature, and thus, the material of the Nakamura container may not be recyclable by conventional means.
Others have provided non-PVC multilayered tubings. For example U.S. Pat. No. 5,562,127 discloses a chlorine-free multilayered tubing material having an inner thermoplastic layer having a Young's modulus from about 2 to about 60 MPa and an outer layer having a Young's modulus of equal to up to about seven times the Young's modulus of the inner layer. (Col. 2, line 33-col. 3, line 8). The outer layer reportedly provides toughness and abrasion resistance. (Col. 2, lines 62-64). However, without special processing conditions the tubing is likely to be too stiff to be compatible with medical infusion pumps such as Baxter's FLO-GARD.RTM..
Therefore, the need exists for medical tubing produced from a polyolefin material having a thermoplastic nature and the desirable characteristics of PVC materials without the elution of plasticizers.